We propose to employ molecular techniques to elucidate the interactions that take place during influenza virus replication. Specifically, viral proteins or virus-specific RNA will be generated from cDNA vectors, thereby allowing the study of specific structure/function relationships. In preliminary experiments, we have succeeded in demonstrating specific binding of viral nucleoprotein (NP) to a synthetic flu-like RNA. We also plan to define the functional domains of the NP and matrix (M) protein that are involved in replication by using reconstituted viral transcription/replication systems. Results obtained in these studies should contribute greatly to a better understanding of the mechanisms operating during influenza virus replication and, therefore, should help in defining strategies for the development of antiviral agents against influenza.